Film forming hard capsule solution

ABSTRACT

A film forming solution usable for the manufacture of an allergen free hard capsule containing pullulan polysaccharide, a neutrally charged hydrophilic amide derived from an amino acid, a rheology modifier, a plasticizer, a chelating agent, and Q.S. amount of water. The film forming solution creates hard capsules that are dimensionally stable with a combination of mechanical strength, resistance to cracking and resiliency. The created hard capsules have a body and a cap that easily engage while producing an oxygen barrier for product contained in the allergen free hard capsules.

FIELD

The current embodiments generally relate to soft or hard capsules madeof polysaccharides for the use in pharmaceuticals and food.

BACKGROUND

There is a need in the art to overcome drawbacks of conventionalpolysaccharide film compositions to make hard capsules for use in thepharmaceutical and vitamin supplement industries.

A need exists to reduce the brittleness of polysaccharide hard capsules,which is prevalent in conventional capsules for very dry fillings. Also,the brittleness of polysaccharides film is due to the existence of “acombined content of mono-, di- and oligosaccharides of 5.0 percent to8.7 percent”. Formulation remedies are needed to overcome the effect ofthese mono, di- and oligo-saccharides.

A further need exists to overcome spot mechanical weakness of pullulanpolysaccharides hard shell capsules that result from clumping, which isattributable to the existence of non-dispersed ultra largepolysaccharides molecules in pullulan powder with molecular weight ofmore than 810 KDa (molecules in pullulan have a degree of polymerization(DP) above 4934 of maltotriose (C6H1205)n units).

A further need exists to accelerate the manufacturing process andimprove its efficiency in order to reduce the high production cost forpolysaccharides capsules.

The present embodiments meet these needs.

BRIEF DESCRIPTION OF THE DRAWINGS

The detailed description will be better understood in conjunction withthe accompanying drawings as follows:

FIG. 1 depicts a photo of a microscopic view of a hard capsule shellsurface with a weak spot according to one or more embodiments.

FIG. 2 depicts a photo of a microscopic view of a smooth, improved filmsurface of a hard capsule shell according to one or more embodiments.

FIG. 3 depicts a film formation and moisture chart according to one ormore embodiments.

FIG. 4 depicts a process according to one or more embodiments.

FIGS. 5A-5J depict the sequence of steps of forming a vegan allergenfree capsules according to one or more embodiments.

FIG. 6 shows ingredients for a Pullulan film with the formula of Example1.

FIG. 7 shows ingredients for a Pullulan film with the formula of Example2.

FIG. 8 shows ingredients for a Pullulan film with the formula of Example3.

FIG. 9 shows ingredients for a Pullulan film with the formula of Example4.

FIG. 10 shows ingredients for a Pullulan film with the formula ofExample 5.

FIG. 11 shows ingredients for a Pullulan film with the formula ofExample 6.

FIG. 12 shows ingredients for a Pullulan film with the formula ofExample 7.

FIG. 13 shows ingredients for a Pullulan film with the formula ofExample 8.

FIG. 14 shows ingredients for a Pullulan film with the formula ofExample 9.

FIG. 15 shows ingredients for a Pullulan film with the formula ofExample 10.

FIG. 16 shows ingredients for a Pullulan film with the formula ofExample 11.

FIG. 17 shows ingredients for a Pullulan film with the formula ofExample 12.

The present embodiments are detailed below with reference to the listedFigures.

DETAILED DESCRIPTION OF THE EMBODIMENTS

Before explaining the present embodiments in detail, it is to beunderstood that the formulation and process are not limited to theparticular embodiments and that it can be practiced or carried out invarious ways.

The embodiments overcome the spot mechanical weakness of polysaccharidesfilm due to clumps formed by ultra large polysaccharides molecules inpullulan powder and reduce the breakage of polysaccharide film fromprior arts.

The embodiments relate to a film forming solution for use in themanufacturing of hard shell capsules for pharmaceutical or food usage.The film forming solution has pullulan polysaccharides with a weightaverage molecular size of 360-480 KDa, containing less than 0.5 percent,preferably less than 0.1 percent polysaccharides molecules that arelarger than 810 KDa. The process of obtaining less than 0.1 percentpolysaccharides molecules that are larger than 810 KDa pullulan powderis possible by applying extra filtration step for removal of such largemolecules.

The embodiments relate to a film forming solution for use in themanufacturing of hard shell capsules for pharmaceutical or food usagehas one or more combinations of neutrally charged hydrophilic amides,preferably derived from amino acids. The neutrally charged hydrophilicamides will form covalent bonds with mono-, di-, and oligo-saccharidesmolecules of pullulan powder, reducing the brittleness, neutralizing theeffects of mono-, di- and oligo-saccharides in pullulan powder on hardshell capsules filled with dry powder. The amount of neutrally chargedhydrophilic amides required in the formula is proportionally linked tothe amount of mono-, di- and oligo-saccharides presented in pullulanpowder.

The embodiments relate to a film forming solution for use in themanufacturing of hard shell capsules for pharmaceutical or food usage.The film forming solution has a pullulan polysaccharide with a weightaverage molecular size of 360-480 KDa, containing less than 0.5 percentmolecules larger than 810 KDa, one or combination of neutrally chargedhydrophilic amides derived from amino acids, one or combination ofrheology modifiers, at least one plasticizer, at least one chelatingagent, and a vegan polishing agent.

The embodiments relate to a hollow dosage form containing activeingredients and ancillary substances, wherein the active ingredientsinclude from 40 percent to 99 percent of pullulan polysaccharide with nomore than 0.5 percent pullulan polysaccharides with a molecular weightgreater than 810 kDa and a neutrally charged hydrophilic amide derivedfrom an amino acid, and wherein the mass ratio of the active ingredientsto the ancillary substances is from 1:19 to 1:999 and is in the form ofan allergen free hard capsule.

In embodiments, the film forming solution usable for the manufacture ofan allergen free hard capsule has about 17 weight percent to about 35weight percent based on the total weight of the solution of pullulanpolysaccharide with no more than 0.5 percent of the pullulanpolysaccharide with a molecular weight greater than 810 kDa, about 0.5weight percent to about 7 weight percent based on the total weight ofthe solution of a neutrally charged hydrophilic amide derived from anamino acid, about 0.1 weight percent to about 1.5 weight percent basedon the total weight of the solution of a rheology modifier, about 0.1weight percent to about 1.5 weight percent based on the total weight ofthe solution of a plasticizer, about 0.01 weight percent to about 0.2weight percent based on the total weight of the solution of a chelatingagent, and a quantity sufficient (Q.S.) amount of purified water,wherein Q.S. stands for the conventional chemical term “quantitysufficient” to create a liquid solution of the powder components in theliquid.

The film forming solution creates allergen free hard capsules that aredimensionally stable with a combination of (i) mechanical strength, (ii)resistance to cracking and (iii) resiliency and wherein the created hardcapsules have a body and cap that easily engage while producing anoxygen barrier for product contained in the allergen free hard capsules.

In embodiments, the film forming solution uses pullulan polysaccharideswith less than 0.5 weight percent, preferably less than 0.1 weightpercent of the polysaccharides with molecular weight greater than 810Kda.

In embodiments of the film forming solution, the neutrally chargedhydrophilic amide derived from amino acids is at least one of: anL-glutamine and an L-asparagine.

In embodiments, a vegan polishing agent can be a plant wax that isapplied to the hard capsules after formation, such as carnauba wax.

In embodiments, the film forming solution uses pullulan polysaccharidesproduced from sugar, corn starch or tapioca starch.

In embodiments, the film forming solution can include a coloring agentin a range from about 0.001 percent to about 2 percent based upon theweight of the solution. The coloring agent can be at least one of azo-,quinophthalone-, triphenylmethane, xanthene- or indigoid dyes, ironoxides or hydroxides, titanium dioxide, natural dyes, and combinationsthereof.

In embodiments, an allergen free hard capsule can be made from the filmforming solution.

Pullulan is a natural, film forming polysaccharides extracellularlyproduced by growing yeast like fungus on starch, sugar or starch base.Hayashibara Company started the commercial production of pullulan in1976, and today, pullulan has been approved as a direct food additive inEU, USA, Japan and many other countries. There are numerous patentsusing pullulan in making moulded articles, edible films, coatings andcapsules.

The pullulan produced by the fungus Aureobasidium pullulans is not oneuniform length polysaccharides, in fact its molecular weight range fromnumber-average molecular weight (Mn) of about 100 to 200 kDa and aweight-average molecular weight (Mw) of about 362 to 480 kDa (Okada etal., 1990). The ultra large molecules existed in pullulan powder isidentified polysaccharides molecules with molecular weight more than 810Kda.

About 1.5 to 2.5 percent of the molecules in pullulan have a degree ofpolymerization (DP) above 4934 maltotriose units (C6H1205). These ultralarge molecule polysaccharides forms invisible clumps to human eyesduring hydration process of pullulan. During the drying process ofpullulan film, the ultra large molecule polysaccharides clumps shrinkmore than its surroundings; thus, making the film around this spotthinner than usual. These thinned spots reduce the mechanical strengthof pullulan film as whole and increase breakage of pullulan capsulesduring filling operation of capsules.

Polysaccharides, such as pullulan and modified starch, can make hard andsoft capsules. Many polysaccharides, such as pullulan, modified starch,carrageenan and alginates, can be utilized in making gelatin-freevegetable capsules. However, for the industrial manufacturing ofpharmaceutical capsules, polysaccharides do not possess thermal gellingproperty they are accustomed to by the industry in gelatin capsulemanufacturing. Attempts were made to create thermal gelling propertiesto polysaccharides by adding gelling agent plus cations.

Hard capsule solely made with just polysaccharides, rheologicalmodifiers with or without cations tend to be less sturdy and easier tobreak due to mechanical bruising than traditional gelatin capsules andhypromellose capsules during filling operation. The capsules made withsuch formula and methods are not uniform in film thickness.

Another problem with pullulan hard capsules are their natural poorsurface gliding performance, which leads to a high opening force of thepre-joint capsules and a high closing force. Traditional methods ofadding surfactants or gliding agents such as sodium lauryl sulfate (SLS)have been vocally objected by more and more consumer groups. A new wayof enhance gliding performance of pullulan capsules is needed.

The present embodiments are an improved formulation for use in hardcapsule manufacture, which overcomes the mechanical weak spots and watermigration from capsules to filling materials that occurs in currentlyavailable capsules.

In embodiments, the following words, phrases, and symbols are generallyintended to have the meanings as set forth below, except to the extentthat the context in which they are used indicates otherwise.

The term “about” as used herein is intended to mean approximately, inthe region of, roughly, or around. When the term “about” is used inconjunction with a numerical range, it modifies that range by extendingthe boundaries above and below the numerical values set forth. Unlessotherwise indicated, it should be understood that the numericalparameters set forth in the following specification and attached claimsare approximations. At the very least, and not as an attempt to limitthe application of the doctrine of equivalents to the scope of theclaims, numerical parameters should be read in light of the number ofreported significant digits and the application of ordinary roundingtechniques.

The term “allergen free” refers to the final hard capsules being free ofthe particular components listed herein: sodium lauryl sulfate,cocoamides, dioctyl sodium sulfosuccinate (DDS), benzalkonium chloride,benzethonium chloride, cetrimide (trimethyltetradecylammonium bromide),fatty acid sugar esters, glyceryl monooleate, polyoxyethylene sorbitanfatty acid esters, polyvinyl alcohol, dimethylpolysiloxane.

The term “capsule” as used herein can refer to either empty or filledcapsule shells whereas “shell” specifically refers to an empty capsule.Since the hard capsule shells described herein can be filled withsubstances in liquid form, the hard capsules may be sealed or bandedaccording to conventional techniques. Alternatively, the hard capsuleshells can be manufactured to have a specific capsule shell design thatprovides certain advantages over conventional techniques, e.g., theability to pre-lock empty caps and bodies, or completing the fillingsteps in a different location, or at a specific time.

The term “chelating agent” as used herein can refer to non-toxic tohuman ingredients that functionally remove cation(s) in solution toprevent interaction of cations interacting with rheology modifyingagents. Preferred chelating agents are lecithin andethylenediaminetetraacetic acid (ETDA) or salts.

The term “coloring agent” as used herein can refer to one or morepharmaceutically acceptable agents, food acceptable coloring agents, ormixtures thereof. The coloring agents may be selected from azo-,quinophthalone-, triphenylmethane-, xanthene- or indigoid dyes, ironoxides or hydroxides, titanium dioxide, or natural dyes and mixturesthereof. Further examples are patent blue V, acid brilliant green BS,red 2G, azorubine, ponceau 4R, amaranth, D+C red 33, D+C red 22, D+C red26, D+C red 28, D+C yellow 10, yellow 2 G, FD+C yellow 5, FD+C yellow 6,FD+C red 3, FD+C red 40, FD+C blue 1, FD+C blue 2, FD+C green 3,brilliant black BN, carbon black, iron oxide black, iron oxide red, ironoxide yellow, titanium dioxide, riboflavin, carotenes, anthocyanines,turmeric, cochineal extract, chlorophyllin, canthaxanthin, caramel,betanin and Candurin® pearlescent pigments. Candurin® is manufacturedand marketed by Merck KGaA®, of Darmstadt, Germany, and consist oftitanium dioxide and/or iron oxide—approved food and pharmaceuticalcolorants in many countries—and potassium aluminum silicate as colorcarrier.

In embodiments, the pharmaceutically acceptable coloring agents, foodacceptable coloring agents, or mixtures thereof are present in an amountranging from about 0 to about 5 percent by weight, e.g., from about 0 toabout 2.5 percent by weight, and from about 0 to about 1.5 percent byweight over the total weight of the aqueous composition.

The term “film forming solution” as used herein can refer to materialused as base for hard capsule shells. Examples include HPMC (e.g. HPMCtypes 2910, 2906 and/or 2208 as defined in USP30-NF25), gelatin,pullulan, PVA and non-enteric starch derivatives, such as hydroxypropylstarch.

The term “hard capsules” as used herein can refer to capsules intendedfor oral administration to human or animal subjects. The hard capsulesdescribed herein can be manufactured using different processes, such asthe dip molding processes discussed below as well as the use ofconventional equipment. As is described in detail below, pin molds canbe dipped into an aqueous-based film forming solution and subsequentlywithdrawn. The film formed on the molding pins surface can then bedried, stripped off the pins and cut to a desired length, therebyobtaining the capsules caps and bodies. Normally, caps and bodies have aside wall, an open end and a closed end. The length of the side wall ofeach of said parts is generally greater than the capsule diameter. Thecapsule caps and bodies can be telescopically joined together so as tomake their side walls partially overlap and obtain a hard capsule shell.

The term “neutrally charged hydrophilic amide” as used herein can referto amides compounds that are neither positively nor negatively charged,are soluble in water, and are hydrophilic. In embodiments, the neutrallycharged hydrophilic amides derived from amino acids are glutamine and/orasparagines, preferably L-glutamine and/or L-asparagine. The amount ofneutrally charged hydrophilic amides derived from amino acids can be inthe amount that is from 0.5 percent to 7 percent in film formingsolution.

The term “optional” or “optionally” as used herein can mean that thesubsequently described event or circumstance may or may not occur, andthat the description includes instances where the event or circumstanceoccurs and instances in which it does not.

The term “pullulan polysaccharide” can refer to polysaccharide polymerconsisting of maltotriose units, also known as a-1,4; a-1,6-glucan.Three glucose units in maltotriose are connected by an a-1,4 glycosidicbond, whereas consecutive maltotriose units are connected to each otherby an a-1,6 glycosidic bond.

The term “rheology modifier” as used herein can refer alginates, agargum, guar gum, locust bean gum, carrageenan, tara gum, gum arabic,ghatti gum, Khaya grandifolia gum, tragacanth gum, karaya gum, pectin,arabian (araban), xanthan, gellen, starch, Konjac mannan, galactomannan,funoran, and other exocellular polysaccharides. The amount of rheologymodifier can preferably be in the range of 0.1 to 1.5 percent by weight.

The term “weight percent” as used herein can mean weight as a percentageof the total weight.

The term “moisture setting system” as used herein can refer to the startof moisture induced solidifying of pullulan solution; pullulan solutionwill start changing from liquid solution phase into solid gel phase asmoisture in solution is reduced to around 20 percent. After the settingstarts, the pullulan solution becomes immobile and will retain its shapeat the point of setting. The solid gel will be dried into solid film asmoisture is further being reduced.

Now turning to the Figures, FIG. 1 depicts a photo of a microscopic viewof a hard capsule shell surface with a weak spot according to one ormore embodiments.

A microscopic view of a capsule 1 surface with a weak spot 2 isillustrated. The weak spot 2 can be about 6 microns to about 30 micronsthinner than normal/preferred capsule thickness.

Weak spots in film make the film more susceptible to mechanical tearing,pressing and twisting comparing with film with no such weak spots, andresulting elevated chances of breakage of the film and capsules formedby such film during normal usage operation of such film and capsules.

The amount of such weak spots depends on the percentage of ultra largepolysaccharides in the pullulan powder, the blending force during thesolution formation process, and the sitting time of the solution. Inindustrial settings of capsule manufacturing, the blending force isgenerally applied as less as possible to reduce air bubbles. The sittingtime of solution is also timed. Therefore, the amount of weak spots inpullulan film is directly linked to the percentage of ultra largemolecules of pullulan powder.

FIG. 2 depicts a photo of a microscopic view of a smooth, improved filmsurface of a hard capsule shell according to one or more embodiments.

FIG. 3 depicts a moisture induced setting system where film formation inrelation to percentage of moisture is charted according to one or moreembodiments.

More specifically, the Figure shows sample one and sample two over timeas viscosity increases against moisture percentage. As the moisturepercentage drop to a given point, the solution starts to gel and thesolution phase changes into solid gel phase. This uniquemoisture-setting property can be utilized in similar manner as tothermal-setting properties of gelatin. Only instead of changing thetemperatures in gelatin solution to trigger setting, reducing moisturein pullulan solution will trigger the setting. This moisture—gellingproperties of pullulan is utilized to manufacturing pullulan capsules inthe embodiments.

The capsules made with the formula of sample one are also subjected toautomatic high speed encapsulation with maximum vacuum power and maximumvolume filling on an NJP 1200 automatic encapsulation machine to testthe capsules' improvement of machine ability. The filling material canbe calcium carbonate powder, and the reduction of number of broken,deformed capsules per 10,000 capsules is recorded as indicator ofimprovements.

In embodiments, the aqueous solution of film compositions can be usedfor the manufacturing of hard capsules by dip molding process withoutthermo setting system like one used by the traditional process of makinghard gelatin capsules. The solution viscosity and rapid reduction ofmoisture level are used to control the flow down of the solution fromthe dipping pins after dipping. Rather than using temperature drop afterdipping the molds into the solution to trigger the starting ofthermos-setting process like the “gum plus cations” setting system, themoisture-setting properties of pullulan polysaccharides that naturallyexists are used, as illustrated in FIG. 3. The shape and the filmthickness of capsules are controlled by combinations of rheologicalmodifiers and moisture removal process rather than by “thermal-setting”.The advantage of the viscosity plus “moisture-setting” method is thattemperature can remain high after the dipping process. The hightemperature can speed up the film forming process and film dryingprocess. Therefore, the rate of moisture removal is improved, and theproduction efficiency can be improved in comparison with productionefficiency using “thermal setting” system, wherein thermal settingrequires the temperature to be dropped below the “setting temperature”at all times during the drying process, because thermal setting can bereversible.

In embodiments, the film forms solutions and the unit dosage forms madefrom it can be used for providing a protective film for agrochemicals,seeds, herbs, foodstuffs, dyestuffs, pharmaceuticals and flavoringagents. The container can be preferably capsules having a capsule bodyand a capsule cap. The capsule halves of the capsules can be preferablysealed with one or more layers of the film forming solution of thepresent embodiments.

In addition to the new composition, the present embodiments specificallyomit the use of select surfactants in the aqueous composition.

Gliding of the capsule is enhanced using natural vegan plant wax aftercapsules are manufactured by the dipping process.

Plant vegan wax, such as carnauba wax, in fine powder can be used whichhas a particle size of 200 US mesh, in the amount of 0.1 percent to 1.0percent to be sprayed on to the capsules made with present composition.This manufacturing process eliminates the need for surfactants requiredto improve pullulan capsules gliding performance.

Further, the pullulan compositions can additionally contain lecithin,glycerin or sorbitol as a plasticizer.

In embodiments, the water of the aqueous composition can be purified ina manner that is acceptable for pharmaceutical uses as defined under USPpurified water in USP32 and USP34-NF29. It will be understood that theaqueous composition described herein allows for non-aqueous solvents intrace amounts.

With these aqueous solutions, hard pullulan capsules can have improvedmechanical strength and good flexibility during filling operation.

In embodiments, the hard capsule shells as described have a shellthickness (after drying to bring the water content of the shell from 9percent to 16 percent by weight over the weight of the shell) from about70 to about 250 μm, e.g., preferably at about 100 μm. Thus, in oneembodiment, the shell thickness may range from about 70 μm to about 150μm.

Typically, sealing or banding techniques can be used where thesetechniques are well-known to any skilled person in the field ofcapsules.

FIG. 4 depicts the process according to one or more embodiments.

The dip molding process for the manufacture of allergen free hardcapsule shells can include, but is not limited to the steps describedbelow. The process can be utilized by a person of ordinary skill in theindustry, and is not limited to a particular order or sequence.

The process can include forming an allergen free solution, as shown instep 100.

The allergen solution can contain 17 weight percent to about 35 weightpercent based on the total weight of the allergen free solution ofpullulan polysaccharide with no more than 0.5 percent of the pullulanpolysaccharide with a molecular weight greater than 810 kDa, 0.5 weightpercent to about 7 weight percent based on the total weight of theallergen free solution of a neutrally charged hydrophilic amide derivedfrom an amino acid, 0.1 weight percent to about 1.5 weight percent basedon the total weight of the allergen free solution of a rheologymodifier, 0.1 weight percent to about 1.5 weight percent based on thetotal weight of the allergen free solution of a plasticizer, 0.01 weightpercent to about 0.2 weight percent based on the total weight of theallergen free solution of a chelating agent, and a Q.S. amount of water.

In embodiments, a hard capsule shell can contain 65 weight percent toabout 99 weight percent based on the total weight of an allergen freesolution of pullulan polysaccharide with no more than 0.5% of thepullulan polysaccharide with a molecular weight greater than 810 kDa,0.5 weight percent to about 15 weight percent based on the total weightof the allergen free solution of a neutrally charged hydrophilic amidederived from an amino acid, 0.3 weight percent to about 4.5 weightpercent based on the total weight of the allergen free solution of arheology modifier, 0.3 weight percent to about 4.5 weight percent basedon the total weight of the allergen free solution of a plasticizer, 0.01weight percent to about 0.6 weight percent based on the total weight ofthe allergen free solution of a chelating agent, and a quantitysufficient (Q.S.) amount of water

The process can include optionally adding a coloring agent to theallergen free solution, as shown in step 102.

The process can include increasing the temperature of the allergen freesolution to a first temperature (T1) forming a heated allergen freesolution, as shown in step 104.

In embodiments, the temperature can range from about 80 degrees Celsiusto about 85 degrees Celsius.

The process can include filtering the heated allergen free solutionforming a filtrate as shown in step 106.

The heated allergen free solution can be filtered using a wovensynthetic cloth filter having a pore size from 10 microns to 20 micronsand a porosity ranging from 45 percent to 65 percent.

The process can include vacuuming the filtrate to remove from 98 percentto 99 percent of air bubbles in the filtrate forming a reduced bubblefiltrate, as shown in step 108.

The process can include cooling the reduced bubble filtrate until thereduced bubble filtrate drops to a second temperature (T2) forming acooled reduced bubble filtrate, as shown in step 110.

In embodiments, the temperature can range from 40 degrees Celsius to 50degrees Celsius.

The process can include dipping the molding pins into the cooled reducedbubble filtrate at least once, as shown in step 112.

The process can include withdrawing the molding pins from the cooledreduced bubble filtrate, as shown in step 114.

The process can include drying the molding pins with cooled reducedbubble filtrate to quickly remove moisture to reach a moisture inducedsetting point to transform the cooled reduced bubble filtrate into asolid phase gel to form hard capsule shells, as shown step 116.

The process can include coating the hard capsule shells with avegetarian polishing agent forming vegan and allergen free hard capsulesthat are dimensionally stable with a combination of (i) mechanicalstrength, (ii) resistance to cracking, and (iii) resiliency, as shown instep 118.

The created vegan and allergen free hard capsules have a body and capthat easily engage while producing an oxygen barrier for product.

FIGS. 5A-5J depict the sequence of steps of forming the vegan allergenfree capsules containing an ingredient.

FIG. 5A depicts the allergen free solution 50 in a container.

FIG. 5B depicts adding a coloring agent 60 to the allergen free solution50.

FIG. 5C depicts increasing the temperature (T1) of the allergen freesolution from about 80 degrees Celsius to about 85 degrees Celsiusforming a heated allergen free solution 51.

FIG. 5D depicts filtering the heated allergen free solution 51 using awoven synthetic cloth filter 52 with a pore size from 10 microns to 20microns forming a filtrate 53 with air bubbles 54.

FIG. 5E depicts vacuuming the filtrate 53 to remove from 98 percent to99 percent of air bubbles 54 in the filtrate using a vacuum pump 56forming a reduced bubble filtrate.

FIG. 5F depicts cooling the reduced bubble filtrate until the reducedbubble filtrate drops in temperature (T2) ranging from 40 degreesCelsius to 50 degrees Celsius forming a cooled reduced bubble filtrate57.

FIG. 5G depicts dipping the molding pins 70 a and 70 b into the cooledreduced bubble filtrate 57.

FIG. 5H depicts withdrawing the molding pins 70 a and 70 b from thecooled reduced bubble filtrate 57 having a layer of cooled filtrate 80 aand 80 b on each molding pin 70 a and 70 b respectively.

FIG. 5I shows the step of drying the molding pins 70 a and 70 b withcooled filtrate to form hard capsule shells 85 a and 85 b.

FIG. 5J depicts coating the hard capsule shells, a body 85 a and a cap85 b with a vegetarian polishing agent 90 forming vegan and allergenfree hard capsules that are dimensionally stable with a combination of(i) mechanical strength, (ii) resistance to cracking and (iii)resiliency, wherein the created vegan and allergen free hard capsuleshave a body and cap that easily engage while producing an oxygen barrierfor product. The body and cap each have different diameters.

EXAMPLES

The following includes but is not limited to examples of film formingsolution usable for the manufacture of an allergen free capsule.

Example 1

Pullulan powder with less than 0.5 percent, preferably less than 0.1percent ultra 5 large molecules, with the formula shown in FIG. 6:

The abbreviation “Pul-N formula” refers to pullulan new formulation

The abbreviation “Pul formula” refers to pullulan regular formulation.

In this example, all the identified ingredients are mixed for 21 minutesin a jacketed vat and then heated with hot water at a temperature of 100degrees Celsius as an aqueous solution to a temperature of 80 degreesCelsius for 10 minutes. The heated and mixed aqueous solution is thenagitated for about 20 minutes with a mechanical agitator having aplurality of blades, such as 2, at a low rpm, for gentle reduced bubblemixing to create a homogenous mixture with few air bubbles.

After creating the homogenous mixture, the homogenous mixture is thenfiltered through a woven synthetic cloth filter having a pore size of 10microns.

The pores can be any number of shapes. The porosity of the filter can be50 percent.

The filtrate is then allowed to cool using a jacketed vat withelectrical cooler system or a similar cooling device, until the filtratedrops in temperature to 40 degrees Celsius in 2 hours forming a cooledfiltrate.

The filtrate temperature drop should drop to the target temperature in atwo hour window.

The cooled filtrate has air bubbles that are then removed using reducedpressure with a vacuum pump. The vacuum eliminates 98 percent of all airbubbles in the cooled filtrate. The air bubble free filtrate can bestored for later use.

The cooled filtrate is surfactant free, such as free of sodium laurylsulfate.

Hard capsules are then formed using the stored air bubble free filtrateby one of various known dipping methods, such as using dipping pins andrepeatedly dipping while cooled filtrate is maintained at a temperaturefrom 40 degrees to 50 degrees Celsius, a thin layer of air bubble freefiltrate will adhere on the surface of pins.

Then, quickly remove the moisture content of the air bubble freefiltrate adhered on the pins by blowing hot and drying air. The airbubble free filtrate layer will start the moisture induced setting andwill change from liquid phase into a solid gel phase. The solid gelphase will further harden to form a hard capsule after further drying.More specifically, in embodiments after dipping, the dipping pins aresubjected to hot air for drying. The hot air can have a temperature of44 degrees Celsius. The hot air can be blown onto the dipping pins fromsix different angles to dry the viscous pullulan solution in the shapeof the dipping pins.

As soon as the surface pullulan forms a film, the pins with film arethen moved into drying tunnels.

Air in the drying tunnels is maintained at a temperature of 43 degreesCelsius and a relative humidity of 15 percent.

The choice of temperature is based on information shown in FIG. 3, whichshows the film formation and moisture chart.

The formed capsule body and cap are then removed from the dipping pinssuch as by cutting and stripping, and then joined into pre-lockposition.

Pre-locked pullulan capsules are sprayed with plant based wax, such ascarnauba wax to improve gliding performance on an encapsulation machineand also improve flow-ability during production process.

The capsule(s) made according to embodiments of Example 1 have improvedpullulan capsule film.

“Brittleness properties” of capsules is defined by calculatingpercentage of capsules that will crack, deform, unable to return to itsoriginal shape after dropping a 15 gram steel piece in a plasticcylinder at a height of 20 cm on each of randomly selected 20 capsules.Brittleness property is a collective indicator of mechanical strength,flexibility and resilience of capsules under mechanical stress.

The capsule(s) made according to embodiments of Example 1 have abrittleness property improved by about 36 percent at ambienttemperatures.

No setting agent is needed in this formulation. No trigger settingagents are needed in this film.

Additionally, this formulation requires no surfactant to maintain thesuspension of ultra large molecules, or as a polishing agent.

The formed capsule of this formation has an improved moisture retentionproperty during storage at ambient temperature. The property to retainits original moisture level keeps the capsule flexible even when verydry ingredients are used inside the capsule for delivery to a subject,reducing chances of interaction between the capsules shell and theingredient that is placed into the domed capsule. The moisture retentionproperty enables the capsule to remain resistant to water withdrawal andadsorption of water into product contained in the capsule.

This moisture retention property prevents crosslinking and migrationwith product in the capsule. The moisture retention property preventsdevelopment of a brittle capsule that either can break or cause otherproduct contamination.

Sodium lauryl sulfate or similar surfactants or gliding agent is notneeded with this capsule formulation. Due to overall environmentalissues and toxicity issues for people, the invention uses plant waxreplacing the need for the sodium lauryl sulfate.

The embodiments satisfy a need for an animal ingredient free naturalcomposition. This is a non-gelatin capsule that vegans can take. Hydroxymethyl propyl cellulose is a semi-synthetic fiber and is not a naturalproduct. This formulation satisfies a need for all natural ingredientscapsule desired by the consumer. This formulation provides a lowerenvironmental impact on society and the environment overall.

Example 2

FIG. 7 shows the ingredients for the Pullulan powder with the formula ofExample 2:

In this example, all the identified ingredients are mixed for 20 minutesin a jacketed vat and then heated with hot water at a temperature of 100degrees Celsius as an aqueous solution to a temperature of 82 degreesCelsius for 20 minutes. The heated and mixed aqueous solution is thenagitated for about 20 minutes with a mechanical agitator having aplurality of blades (2) for gentle reduced bubble mixing to create ahomogenous mixture with few air bubbles.

After creating the homogenous mixture, the homogenous mixture is thenfiltered through a woven synthetic cloth filter having a pore size from20 microns. The pores can be any number of shapes. The porosity of thefilter can range from 45 percent to 65 percent.

The filtrate has air bubbles that are then removed using reducedpressure with a vacuum pump. The vacuum eliminates from 98 percent to 99percent of all air bubbles in the filtrate. The air bubble free filtratecan be stored for later use.

The filtrate is then allowed to cool using a jacketed vat withelectrical cooler system or a similar cooling device, until the filtratedrops in temperature to 45 degrees Celsius forming a cooled filtrate.

The filtrate temperature drop should drop to the target temperature in atwo hour window.

The cooled filtrate is surfactant free, such as free of sodium laurylsulfate.

Hard capsules are then formed using the stored air bubble free filtrateby one of various known dipping methods, such as using dipping pins andrepeatedly dipping while cooled filtrate is maintained at a temperaturefrom 40 degrees to 50 degrees Celsius, a thin layer of air bubble freefiltrate will adhere on the surface of pins.

Then, quickly remove the moisture content of the air bubble freefiltrate adhered on the pins by blowing hot and drying air. The airbubble free filtrate layer will start the moisture induced setting andwill change from liquid phase into a solid gel phase. The solid gelphase will further change to harden to a hard capsule after furtherdrying. More specifically, after dipping, the dipping pins are subjectedto hot air for drying. The hot air can have a temperature of 42 degreesCelsius. The hot air can be blown onto the dipping pins from fourdifferent angles to dry the viscous pullulan solution in the shape ofthe dipping pins.

As soon as the surface pullulan forms a film, the pins with film arethen moved into drying tunnels.

Air in the drying tunnels is maintained at a temperature from 39 degreesCelsius and a relative humidity from 15 percent to 28 percent.

The choice of temperature is based on information shown in FIG. 3, whichshows the film formation and moisture chart.

The formed capsule body and cap are the removed from the dipping pinssuch as by cutting and stripping, and then joined into a pre-lockposition.

Pre-locked pullulan capsules are sprayed with plant based wax, such ascarnauba wax to improve gliding performance on an encapsulation machineand also improve flow-ability during production process.

The capsule(s) made according to embodiments of Example 2 have improvedpullulan capsule film.

The capsule(s) made according to embodiments of Example 2 have abrittleness property improved by about 37 percent at ambienttemperatures.

No setting agent is needed in this formulation. No trigger settingagents are needed in this film.

Additionally, this formulation requires no surfactant to maintain thesuspension of ultra large molecules, or as a polishing agent.

The formed capsule of this formation has improved moisture retentionproperty during storage at ambient temperature. The moisture loss atambient temperature reduced by 23 percent.

Example 3

FIG. 8 shows the ingredients for the Pullulan film with the formula ofExample 3:

In this example, all the identified ingredients are mixed for 20 minutesin a jacketed vat and then heated with hot water at a temperature of 100degrees Celsius as an aqueous solution to a temperature of 82 degreesCelsius for 20 minutes. The heated and mixed aqueous solution is thenagitated for about 20 minutes with a mechanical agitator having aplurality of blades (2) for gentle reduced bubble mixing to create ahomogenous mixture with few air bubbles.

After creating the homogenous mixture, the homogenous mixture is thenfiltered through a woven synthetic cloth filter having a pore size from20 microns. The pores can be any number of shapes. The porosity of thefilter can range from 45 percent to 65 percent.

The filtrate has air bubbles that are then removed using reducedpressure with a vacuum pump. The vacuum eliminates from 98 percent to 99percent of all air bubbles in the filtrate. The air bubble free filtratecan be stored for later use.

The filtrate is then allowed to cool using a jacketed vat withelectrical cooler system or a similar cooling device, until the filtratedrops in temperature to 45 degrees Celsius forming a cooled filtrate.

The filtrate temperature drop should drop to the target temperature in atwo hour window.

The cooled filtrate is surfactant free, such as free of sodium laurylsulfate.

Hard capsules are then formed using the stored air bubble free filtrateby one of various known dipping methods, such as using dipping pins andrepeatedly dipping and drying the pins into the air bubble free filtrateallowing the layers to harden to a hard capsule,

More specifically, in embodiments after dipping, the dipping pins aresubjected to hot air for drying. The hot air can have a temperature of44 degrees Celsius. The hot air can be blown onto the dipping pins fromfour different angles to dry the viscous pullulan solution in the shapeof the dipping pins.

As soon as the surface pullulan forms a film, the pins with film arethen moved into drying tunnels.

Air in the drying tunnels is maintained at a temperature from 36 degreesCelsius and a relative humidity from 15 percent to 28 percent.

The choice of temperature is based on information shown in FIG. 3, whichshows the film formation and moisture chart.

The formed capsule body and cap are the removed from the dipping pinssuch as by cutting and stripping, and then joined into a pre-lockposition.

Pre-locked pullulan capsules are sprayed with plant based wax, such ascarnauba wax to improve gliding performance on an encapsulation machineand also improve flow-ability during production process.

The capsule(s) made according to embodiments of Example 3 have improvedpullulan capsule film.

The capsule(s) made according to embodiments of Example 3 have abrittleness property improved by about 14 percent at ambienttemperatures.

No setting agent is needed in this formulation. No trigger settingagents are needed in this film.

Additionally, this formulation requires no surfactant to maintain thesuspension of ultra large molecules, or as a polishing agent.

The formed capsule of this formation has improved moisture retentionproperty during storage at ambient temperature. The moisture loss atambient temperature reduced by 6 percent.

Example 4

FIG. 9 shows the ingredients for the Pullulan film with the formula ofExample 4:

In this example, all the identified ingredients are mixed from 20minutes in a jacketed vat and then heated with hot water at atemperature between 100 degrees Celsius as an aqueous solution to atemperature from 82 degrees Celsius for 20 minutes. The heated and mixedaqueous solution is then agitated for about 20 minutes with a mechanicalagitator having a plurality of blades (2) for gentle reduced bubblemixing to create a homogenous mixture with few air bubbles.

After creating the homogenous mixture, the homogenous mixture is thenfiltered through a woven synthetic cloth filter having a pore size from20 microns. The pores can be any number of shapes. The porosity of thefilter can range from 45 percent to 65 percent.

The filtrate has air bubbles that are then removed using reducedpressure with a vacuum pump. The vacuum eliminates from 98 percent to 99percent of all air bubbles in the filtrate. The air bubble free filtratecan be stored for later use.

The filtrate is then allowed to cool using a jacketed vat withelectrical cooler system or a similar cooling device, until the filtratedrops in temperature to 45 degrees Celsius forming a cooled filtrate.

The filtrate temperature drop should drop to the target temperature in atwo hour window.

The cooled filtrate is surfactant free, such as free of sodium laurylsulfate.

Hard capsules are then formed using the stored air bubble free filtrateby one of various known dipping methods, such as using dipping pins andrepeatedly dipping and drying the pins into the air bubble free filtrateallowing the layers to harden to a hard capsule,

More specifically, in embodiments after dipping, the dipping pins aresubjected to hot air for drying. The hot air can have a temperature of42 degrees Celsius. The hot air can be blown onto the dipping pins fromfour different angles to dry the viscous pullulan solution in the shapeof the dipping pins.

As soon as the surface pullulan forms a film, the pins with film arethen moved into drying tunnels.

Air in the drying tunnels is maintained at a temperature of 39 degreesCelsius and a relative humidity from 15 percent to 28 percent.

The choice of temperature is based on information shown in FIG. 3, whichshows the film formation and moisture chart.

The formed capsule body and cap are the removed from the dipping pinssuch as by cutting and stripping, and then joined into a pre-lockposition.

Pre-locked pullulan capsules are sprayed with plant based wax, such ascarnauba wax to improve gliding performance on an encapsulation machineand also improve flow-ability during production process.

The capsule(s) made according to embodiments of Example 4 have improvedpullulan capsule film.

The capsule(s) made according to embodiments of Example 4 have abrittleness property improved by about 26 percent at ambienttemperatures.

No setting agent is needed in this formulation. No trigger settingagents are needed in this film.

Additionally, this formulation requires no surfactant to maintain thesuspension of ultra large molecules, or as a polishing agent.

The formed capsule of this formation has improved moisture retentionproperty during storage at ambient temperature. The moisture loss atambient temperature reduced by 16 percent.

Example 5

FIG. 10 shows the ingredients for the Pullulan film with the formula ofExample 5:

In this example, all the identified ingredients are mixed for 20 minutesin a jacketed vat and then heated with hot water at a temperature of 100degrees Celsius as an aqueous solution to a temperature of 82 degreesCelsius for 20 minutes. The heated and mixed aqueous solution is thenagitated for about 30 minutes with a mechanical agitator having aplurality of blades (2) for gentle reduced bubble mixing to create ahomogenous mixture with few air bubbles.

After creating the homogenous mixture, the homogenous mixture is thenfiltered through a woven synthetic cloth filter having a pore size from20 microns. The pores can be any number of shapes. The porosity of thefilter can range from 45 percent to 65 percent.

The filtrate has air bubbles that are then removed using reducedpressure with a vacuum pump. The vacuum eliminates from 98 percent to 99percent of all air bubbles in the filtrate. The air bubble free filtratecan be stored for later use.

The filtrate is then allowed to cool using a jacketed vat withelectrical cooler system or a similar cooling device, until the filtratedrops in temperature to between 45 degrees Celsius forming a cooledfiltrate.

The filtrate temperature drop should drop to the target temperature in atwo hour window.

The cooled filtrate is surfactant free, such as free of sodium laurylsulfate.

Hard capsules are then formed using the stored air bubble free filtrateby one of various known dipping methods, such as using dipping pins andrepeatedly dipping and drying the pins into the air bubble free filtrateallowing the layers to harden to a hard capsule.

More specifically, in embodiments after dipping, the dipping pins aresubjected to hot air for drying. The hot air can have a temperature of42 degrees Celsius. The hot air can be blown onto the dipping pins fromfour different angles to dry the viscous pullulan solution in the shapeof the dipping pins.

As soon as the surface pullulan forms a film, the pins with film arethen moved into drying tunnels.

Air in the drying tunnels is maintained at a temperature of 39 degreesCelsius and a relative humidity from 15 percent to 28 percent.

The choice of temperature is based on information shown in FIG. 3, whichshows the film formation and moisture chart.

The formed capsule body and cap are the removed from the dipping pinssuch as by cutting and stripping, and then joined into a pre-lockposition.

Pre-locked pullulan capsules are sprayed with plant based wax, such ascarnauba wax to improve gliding performance on an encapsulation machineand also improve flow-ability during production process.

The capsule(s) made according to embodiments of Example 5 have improvedpullulan capsule film.

The capsule(s) made according to embodiments of Example 5 have abrittleness property improved by about 9 percent at ambienttemperatures.

No setting agent is needed in this formulation. No trigger settingagents are needed in this film.

Additionally, this formulation requires no surfactant to maintain thesuspension of ultra large molecules, or as a polishing agent.

The formed capsule of this formation has improved moisture retentionproperty during storage at ambient temperature. The moisture loss atambient temperature reduced by 4 percent.

Example 6

FIG. 11 shows the ingredients for the Pullulan film with the formula ofExample 6:

In this example, all the identified ingredients are mixed for 20 minutesin a jacketed vat and then heated with hot water at a temperature of 100degrees Celsius as an aqueous solution to a temperature of 82 degreesCelsius for 20 minutes. The heated and mixed aqueous solution is thenagitated for about 20 minutes with a mechanical agitator having aplurality of blades (2) for gentle reduced bubble mixing to create ahomogenous mixture with few air bubbles.

After creating the homogenous mixture, the homogenous mixture is thenfiltered through a woven synthetic cloth filter having a pore size from20 microns. The pores can be any number of shapes. The porosity of thefilter can range from 45 percent to 65 percent.

The filtrate has air bubbles that are then removed using reducedpressure with a vacuum pump. The vacuum eliminates from 98 percent to 99percent of all air bubbles in the filtrate. The air bubble free filtratecan be stored for later use.

The filtrate is then allowed to cool using a jacketed vat withelectrical cooler system or a similar cooling device, until the filtratedrops in temperature to between 45 degrees Celsius forming a cooledfiltrate.

The filtrate temperature drop should drop to the target temperature in atwo hour window.

The cooled filtrate is surfactant free, such as free of sodium laurylsulfate.

Hard capsules are then formed using the stored air bubble free filtrateby one of various known dipping methods, such as using dipping pins andrepeatedly dipping and drying the pins into the air bubble free filtrateallowing the layers to harden to a hard capsule,

More specifically, in embodiments after dipping, the dipping pins aresubjected to hot air for drying. The hot air can have a temperature of42 degrees Celsius. The hot air can be blown onto the dipping pins fromfour different angles to dry the viscous pullulan solution in the shapeof the dipping pins.

As soon as the surface pullulan forms a film, the pins with film arethen moved into drying tunnels.

Air in the drying tunnels is maintained at a temperature from 39 degreesCelsius and a relative humidity from 15 percent to 28 percent.

The choice of temperature is based on information shown in FIG. 3, whichshows the film formation and moisture chart.

The formed capsule body and cap are the removed from the dipping pinssuch as by cutting and stripping, and then joined into a pre-lockposition.

Pre-locked pullulan capsules are sprayed with plant based wax, such ascarnauba wax to improve gliding performance on an encapsulation machineand also improve flow-ability during production process.

The capsule(s) made according to embodiments of Example 6 have improvedpullulan capsule film.

The capsule(s) made according to embodiments of Example 6 have abrittleness property improved by about 26 percent at ambienttemperatures.

No setting agent is needed in this formulation. No trigger settingagents are needed in this film.

Additionally, this formulation requires no surfactant to maintain thesuspension of ultra large molecules, or as a polishing agent.

The formed capsule of this formation has improved moisture retentionproperty during storage at ambient temperature. The moisture loss atambient temperature reduced by 16 percent.

Example 7

FIG. 12 shows the ingredients for the Pullulan film with the formula ofExample 7:

In this example, all the identified ingredients are mixed for 20 minutesin a jacketed vat and then heated with hot water at a temperature of 100degrees Celsius as an aqueous solution to a temperature of 82 degreesCelsius for 20 minutes. The heated and mixed aqueous solution is thenagitated for about 25 minutes with a mechanical agitator having aplurality of blades (2) for gentle reduced bubble mixing to create ahomogenous mixture with few air bubbles.

After creating the homogenous mixture, the homogenous mixture is thenfiltered through a woven synthetic cloth filter having a pore size from20 microns. The pores can be any number of shapes. The porosity of thefilter can range from 45 percent to 65 percent.

The filtrate has air bubbles that are then removed using reducedpressure with a vacuum pump. The vacuum eliminates from 98 percent to 99percent of all air bubbles in the filtrate. The air bubble free filtratecan be stored for later use.

The filtrate is then allowed to cool using a jacketed vat withelectrical cooler system or a similar cooling device, until the filtratedrops in temperature to 45 degrees Celsius forming a cooled filtrate.

The filtrate temperature drop should drop to the target temperature in atwo hour window.

The cooled filtrate is surfactant free, such as free of sodium laurylsulfate.

Hard capsules are then formed using the stored air bubble free filtrateby one of various known dipping methods, such as using dipping pins andrepeatedly dipping and drying the pins into the air bubble free filtrateallowing the layers to harden to a hard capsule.

More specifically, after dipping, the dipping pins are subjected to hotair for drying.

The hot air can have a temperature of 42 degrees Celsius. The hot aircan be blown onto the dipping pins from four different angles to dry theviscous pullulan solution in the shape of the dipping pins.

As soon as the surface pullulan forms a film, the pins with film arethen moved into drying tunnels.

Air in the drying tunnels is maintained at a temperature of 39 degreesCelsius and a relative humidity from 15 percent to 28 percent.

The choice of temperature is based on information shown in FIG. 3, whichshows the film formation and moisture chart.

The formed capsule body and cap are the removed from the dipping pinssuch as by cutting and stripping, and then joined into a pre-lockposition.

Pre-locked pullulan capsules are sprayed with plant based wax, such ascarnauba wax to improve gliding performance on an encapsulation machineand also improve flow-ability during production process.

The capsule(s) made according to embodiments of Example 7 have improvedpullulan capsule film.

The capsule(s) made according to embodiments of Example 7 have abrittleness property improved by about 35 percent at ambienttemperatures.

No setting agent is needed in this formulation. No trigger settingagents are needed in this film.

Additionally, this formulation requires no surfactant to maintain thesuspension of ultra large molecules, or as a polishing agent.

The formed capsule of this formation has improved moisture retentionproperty during storage at ambient temperature. The moisture loss atambient temperature reduced by 18 percent.

Example 8

FIG. 13 shows the ingredients for the Pullulan film with the formula ofExample 8:

In this example, all the identified ingredients are mixed for 20 minutesin a jacketed vat and then heated with hot water at a temperature of 100degrees Celsius as an aqueous solution to a temperature of 82 degreesCelsius for 20 minutes. The heated and mixed aqueous solution is thenagitated for about 20 minutes with a mechanical agitator having aplurality of blades (2) for gentle reduced bubble mixing to create ahomogenous mixture with few air bubbles.

After creating the homogenous mixture, the homogenous mixture is thenfiltered through a woven synthetic cloth filter having a pore size from20 microns. The pores can be any number of shapes. The porosity of thefilter can range from 45 percent to 65 percent.

The filtrate has air bubbles that are then removed using reducedpressure with a vacuum pump. The vacuum eliminates from 98 percent to 99percent of all air bubbles in the filtrate. The air bubble free filtratecan be stored for later use.

The filtrate is then allowed to cool using a jacketed vat withelectrical cooler system or a similar cooling device, until the filtratedrops in temperature to 45 degrees Celsius forming a cooled filtrate.

The filtrate temperature drop should drop to the target temperature in atwo hour window.

The cooled filtrate is surfactant free, such as free of sodium laurylsulfate.

Hard capsules are then formed using the stored air bubble free filtrateby one of various known dipping methods, such as using dipping pins andrepeatedly dipping and drying the pins into the air bubble free filtrateallowing the layers to harden to a hard capsule.

More specifically, in embodiments after dipping, the dipping pins aresubjected to hot air for drying. The hot air can have a temperature of42 degrees Celsius. The hot air can be blown onto the dipping pins fromfour different angles to dry the viscous pullulan solution in the shapeof the dipping pins.

As soon as the surface pullulan forms a film, the pins with film arethen moved into drying tunnels.

Air in the drying tunnels is maintained at a temperature of 39 degreesCelsius and a relative humidity from 15 percent to 28 percent.

The choice of temperature is based on information shown in FIG. 3, whichshows the film formation and moisture chart.

The formed capsule body and cap are then removed from the dipping pinssuch as by cutting and stripping, and then joined into a pre-lockposition.

Pre-locked pullulan capsules are sprayed with plant based wax, such ascarnauba wax to improve gliding performance on an encapsulation machineand also improve flow-ability during production process.

The capsule(s) made according to embodiments of Example 8 have improvedpullulan capsule film.

The capsule(s) made according to embodiments of Example 8 have abrittleness property improved by about 41 percent at ambienttemperatures.

No setting agent is needed in this formulation. No trigger settingagents are needed in this film.

Additionally, this formulation requires no surfactant to maintain thesuspension of ultra large molecules, or as a polishing agent.

The formed capsule of this formation has improved moisture retentionproperty during storage at ambient temperature. The moisture loss atambient temperature reduced by 23 percent.

Example 9

FIG. 14 shows the ingredients for the Pullulan film with the formula ofExample 9:

In this example, all the identified ingredients are mixed for 20 minutesin a jacketed vat and then heated with hot water at a temperature of 100degrees Celsius as an aqueous solution to a temperature of 82 degreesCelsius for 20 minutes. The heated and mixed aqueous solution is thenagitated for about 25 minutes with a mechanical agitator having aplurality of blades (2) for gentle reduced bubble mixing to create ahomogenous mixture with few air bubbles.

After creating the homogenous mixture, the homogenous mixture is thenfiltered through a woven synthetic cloth filter having a pore size from20 microns. The pores can be any number of shapes. The porosity of thefilter can range from 45 percent to 65 percent.

The filtrate has air bubbles that are then removed using reducedpressure with a vacuum pump. The vacuum eliminates from 98 percent to 99percent of all air bubbles in the filtrate. The air bubble free filtratecan be stored for later use.

The filtrate is then allowed to cool using a jacketed vat withelectrical cooler system or a similar cooling device, until the filtratedrops in temperature to 45 degrees Celsius forming a cooled filtrate.

The filtrate temperature drop should drop to the target temperature in atwo hour window.

The cooled filtrate is surfactant free, such as free of sodium laurylsulfate.

Hard capsules are then formed using the stored air bubble free filtrateby one of various known dipping methods, such as using dipping pins andrepeatedly dipping and drying the pins into the air bubble free filtrateallowing the layers to harden to a hard capsule.

More specifically, in embodiments after dipping, the dipping pins aresubjected to hot air for drying. The hot air can have a temperature of42 degrees Celsius. The hot air can be blown onto the dipping pins fromfour different angles to dry the viscous pullulan solution in the shapeof the dipping pins.

As soon as the surface pullulan forms a film, the pins with film arethen moved into drying tunnels.

Air in the drying tunnels is maintained at a temperature of 39 degreesCelsius and a relative humidity from 15 percent to 28 percent.

The choice of temperature is based on information shown in FIG. 3, whichshows the film formation and moisture chart.

The formed capsule body and cap are the removed from the dipping pinssuch as by cutting and stripping, and then joined into a pre-lockposition.

Pre-locked pullulan capsules are sprayed with plant based wax, such ascarnauba wax to improve gliding performance on an encapsulation machineand also improve flow-ability during production process.

The capsule(s) made according to embodiments of Example 9 have improvedpullulan capsule film.

The capsule(s) made according to embodiments of Example 9 have abrittleness property improved by about 31 percent at ambienttemperatures.

No setting agent is needed in this formulation. No trigger settingagents are needed in this film.

Additionally, this formulation requires no surfactant to maintain thesuspension of ultra large molecules, or as a polishing agent.

The formed capsule of this formation has improved moisture retentionproperty during storage at ambient temperature. The moisture loss atambient temperature reduced by 20 percent.

Example 10

FIG. 15 shows the ingredients for the Pullulan film with the formula ofExample 10:

In this example, all the identified ingredients are mixed for 20 minutesin a jacketed vat and then heated with hot water at a temperature of 100degrees Celsius as an aqueous solution to a temperature of 82 degreesCelsius for 20 minutes. The heated and mixed aqueous solution is thenagitated with a mechanical agitator for about 30 minutes having aplurality of blades (2) for gentle reduced bubble mixing to create ahomogenous mixture with few air bubbles.

After creating the homogenous mixture, the homogenous mixture is thenfiltered through a woven synthetic cloth filter having a pore size from20 microns. The pores can be any number of shapes. The porosity of thefilter can range from 45 percent to 65 percent.

The filtrate has air bubbles that are then removed using reducedpressure with a vacuum pump. The vacuum eliminates from 98 percent to 99percent of all air bubbles in the filtrate. The air bubble free filtratecan be stored for later use.

The filtrate is then allowed to cool using a jacketed vat withelectrical cooler system or a similar cooling device, until the filtratedrops in temperature to 45 degrees Celsius forming a cooled filtrate.

The filtrate temperature drop should drop to the target temperature in atwo hour window.

The cooled filtrate is surfactant free, such as free of sodium laurylsulfate.

Hard capsules are then formed using the stored air bubble free filtrateby one of various known dipping methods, such as using dipping pins andrepeatedly dipping and drying the pins into the air bubble free filtrateallowing the layers to harden to a hard capsule.

More specifically, in embodiments after dipping, the dipping pins aresubjected to hot air for drying. The hot air can have a temperature of42 degrees Celsius. The hot air can be blown onto the dipping pins fromfour different angles to dry the viscous pullulan solution in the shapeof the dipping pins.

As soon as the surface pullulan forms a film, the pins with film arethen moved into drying tunnels.

Air in the drying tunnels is maintained at a temperature from 39 degreesCelsius and a relative humidity from 15 percent to 28 percent.

The choice of temperature is based on information shown in FIG. 3, whichshows the film formation and moisture chart.

The formed capsule body and cap are the removed from the dipping pinssuch as by cutting and stripping, and then joined into a pre-lockposition.

Pre-locked pullulan capsules are sprayed with plant based wax, such ascarnauba wax to improve gliding performance on an encapsulation machineand also improve flow-ability during production process.

The capsule(s) made according to embodiments of Example 10 have improvedpullulan capsule film.

The capsule(s) made according to embodiments of Example 10 have abrittleness property improved by about 38 percent at ambienttemperatures.

No setting agent is needed in this formulation. No trigger settingagents are needed in this film.

Additionally, this formulation requires no surfactant to maintain thesuspension of ultra large molecules, or as a polishing agent.

The formed capsule of this formation has improved moisture retentionproperty during storage at ambient temperature. The moisture loss atambient temperature reduced by 21 percent.

Example 11

FIG. 16 shows the ingredients for the Pullulan film with the formula ofExample 11:

In this example, all the identified ingredients are mixed for 20 minutesin a jacketed vat and then heated with hot water at a temperature of 100degrees Celsius as an aqueous solution to a temperature of 82 degreesCelsius for 20 minutes. The heated and mixed aqueous solution is thenagitated for about 30 minutes with a mechanical agitator having aplurality of blades (2) for gentle reduced bubble mixing to create ahomogenous mixture with few air bubbles.

After creating the homogenous mixture, the homogenous mixture is thenfiltered through a woven synthetic cloth filter having a pore size from20 microns. The pores can be any number of shapes. The porosity of thefilter can range from 45 percent to 65 percent.

The filtrate has air bubbles that are then removed using reducedpressure with a vacuum pump. The vacuum eliminates from 98 percent to 99percent of all air bubbles in the filtrate. The air bubble free filtratecan be stored for later use.

The filtrate is then allowed to cool using a jacketed vat withelectrical cooler system or a similar cooling device, until the filtratedrops in temperature to 45 degrees Celsius forming a cooled filtrate.

The filtrate temperature drop should drop to the target temperature in atwo hour window.

The cooled filtrate is surfactant free, such as free of sodium laurylsulfate.

Hard capsules are then formed using the stored air bubble free filtrateby one of various known dipping methods, such as using dipping pins andrepeatedly dipping and drying the pins into the air bubble free filtrateallowing the layers to harden to a hard capsule,

More specifically, in embodiments after dipping, the dipping pins aresubjected to hot air for drying. The hot air can have a temperature of42 degrees Celsius. The hot air can be blown onto the dipping pins fromfour different angles to dry the viscous pullulan solution in the shapeof the dipping pins.

As soon as the surface pullulan forms a film, the pins with film arethen moved into drying tunnels.

Air in the drying tunnels is maintained at a temperature from 39 degreesCelsius and a relative humidity from 15 percent to 28 percent.

The choice of temperature is based on information shown in FIG. 3, whichshows the film formation and moisture chart.

The formed capsule body and cap are the removed from the dipping pinssuch as by cutting and stripping, and then joined into a pre-lockposition.

Pre-locked pullulan capsules are sprayed with plant based wax, such ascarnauba wax to improve gliding performance on an encapsulation machineand also improve flow-ability during production process.

The capsule(s) made according to embodiments of Example 11 have improvedpullulan capsule film.

The capsule(s) made according to embodiments of Example 11 have abrittleness property improved by about 33 percent at ambienttemperatures.

No setting agent is needed in this formulation. No trigger settingagents are needed in this film.

Additionally, this formulation requires no surfactant to maintain thesuspension of ultra large molecules, or as a polishing agent.

The formed capsule of this formation has improved moisture retentionproperty during storage at ambient temperature. The moisture loss atambient temperature reduced by 16 percent.

Example 12

FIG. 17 shows the ingredients for the Pullulan film with the formula ofExample 12:

In this example, all the identified ingredients are mixed for 20 minutesin a jacketed vat and then heated with hot water at a temperaturebetween 100 degrees Celsius as an aqueous solution to a temperature of82 degrees Celsius for 20 minutes. The heated and mixed aqueous solutionis then agitated for about 30 minutes with a mechanical agitator havinga plurality of blades (2) for gentle reduced bubble mixing to create ahomogenous mixture with few air bubbles.

After creating the homogenous mixture, the homogenous mixture is thenfiltered through a woven synthetic cloth filter having a pore size from20 microns. The pores can be any number of shapes. The porosity of thefilter can range from 45 percent to 65 percent.

The filtrate has air bubbles that are then removed using reducedpressure with a vacuum pump. The vacuum eliminates from 98 percent to 99percent of all air bubbles in the filtrate. The air bubble free filtratecan be stored for later use.

The filtrate is then allowed to cool using a jacketed vat withelectrical cooler system or a similar cooling device, until the filtratedrops in temperature to 45 degrees Celsius forming a cooled filtrate.

The filtrate temperature drop should drop to the target temperature in atwo hour window.

The cooled filtrate is surfactant free, such as free of sodium laurylsulfate.

Hard capsules are then formed using the stored air bubble free filtrateby one of various known dipping methods, such as using dipping pins andrepeatedly dipping and drying the pins into the air bubble free filtrateallowing the layers to harden to a hard capsule.

More specifically, after dipping, the dipping pins are subjected to hotair for drying. The hot air can have a temperature of 42 degreesCelsius. The hot air can be blown onto the dipping pins from fourdifferent angles to dry the viscous pullulan solution in the shape ofthe dipping pins.

As soon as the surface pullulan forms a film, the pins with film arethen moved into drying tunnels.

Air in the drying tunnels is maintained at a temperature from 39 degreesCelsius and a relative humidity from 15 percent to 28 percent.

The choice of temperature is based on information shown in FIG. 3, whichshows the film formation and moisture chart.

The formed capsule body and cap are the removed from the dipping pinssuch as by cutting and stripping, and then joined into a pre-lockposition.

Pre-locked pullulan capsules are sprayed with plant based wax, such ascarnauba wax to improve gliding performance on an encapsulation machineand also improve flow-ability during production process.

The capsule(s) made according to embodiments of Example 12 have improvedpullulan capsule film.

The capsule(s) made according to embodiments of Example 12 have abrittleness property improved by about 31 percent at ambienttemperatures.

No setting agent is needed in this formulation. No trigger settingagents are needed in this film.

Additionally, this formulation requires no surfactant to maintain thesuspension of ultra large molecules, or as a polishing agent.

The formed capsule of this formation has improved moisture retentionproperty during storage at ambient temperature. The moisture loss atambient temperature reduced by 16 percent.

While these embodiments have been described with emphasis on theembodiments, it should be understood that within the scope of theappended claims, the embodiments might be practiced other than asspecifically described herein.

What is claimed is:
 1. A hollow dosage form containing activeingredients and ancillary substances, wherein the active ingredientsinclude from 40 percent to 99 percent of pullulan polysaccharide with nomore than 0.5 percent pullulan polysaccharide with a molecular weightgreater than 810 Kda and a neutrally charged hydrophilic amide derivedfrom an amino acid, wherein the mass ratio of the active ingredients tothe ancillary substances is from 1:19 to 1:999 and is in the form of anallergen free hard capsule.
 2. A film forming solution usable for amanufacture of allergen free hard capsules using a faster and moreefficient moisture induced setting system to start the transformation ofthe film forming solution from a liquid phase into a solid gel phasecomprising: a. 17 weight percent to 35 weight percent based on the totalweight of the film forming solution of pullulan polysaccharide with nomore than 0.5 percent of the pullulan polysaccharide with a molecularweight greater than 810 Kda; b. 0.5 weight percent to 7 weight percentbased on the total weight of the film forming solution of a neutrallycharged hydrophilic amide derived from an amino acid; c. 0.1 weightpercent to 1.5 weight percent based on the total weight of the filmforming solution of a rheology modifier; d. 0.1 weight percent to 1.5weight percent based on the total weight of the film forming solution ofa plasticizer; e. 0.01 weight percent to about 0.2 weight percent basedon the total weight of the film forming solution of a chelating agent;f. a quantity sufficient (Q.S.) amount of water; wherein the filmforming solution creating hard capsules that are dimensionally stablewith a combination of mechanical strength, resistance to cracking andresiliency, and wherein created allergen free hard capsules have a bodyand a cap that easily engage while producing an oxygen barrier forproduct contained in the allergen free hard capsules.
 3. The filmforming solution of claim 2, wherein the pullulan polysaccharidecomprises less than 0.1 weight percent with the molecular weight greaterthan 810 Kda.
 4. The film forming solution of claim 2, wherein theneutrally charged hydrophilic amide derived from the amino acid is atleast one of: an L-glutamine and an L-asparagine.
 5. The film formingsolution of claim 2, comprising a polishing agent of plant wax that isapplied to the hard capsules after formation.
 6. The film formingsolution of claim 2, wherein the pullulan polysaccharide is producedfrom at least one of: a sugar, a corn starch, and a tapioca starch base.7. The film forming solution of claim 2, further comprising a coloringagent in a range from 0.001 percent to 2 percent based upon the weightof the film forming solution.
 8. The film forming solution of claim 7,wherein the coloring agent comprises at least one of azo-,quinophthalone-, triphenylmethane, xanthene- or indigoid dyes, ironoxides or hydroxides, titanium dioxide, natural dyes, and combinationsthereof.